Taurine Suppression of Central Amygdala GABAergic Inhibitory Signaling via Glycine Receptors Is Disrupted in Alcohol Dependence

Abstract

Background: Alcohol use disorder (AUD) increases brain stress systems while suppressing reward system functioning. One expression of stress system recruitment is elevated GABAergic activity in the central amygdala (CeA), which is involved in the excessive drinking seen with AUD. The sulfonic amino acid taurine, a glycine receptor partial agonist, modulates GABAergic activity in the rewarding effects of alcohol. Despite taurine abundance in the amygdala, its role in the dysregulation of GABAergic activity associated with AUD has not been studied. Thus, here, we evaluated the effects of taurine on locally stimulated GABAergic neurotransmission in the CeA of na€ ıve-and alcohol-dependent rats.Methods: We recorded intracellularly from CeA neurons of na€ ıve-and alcohol-dependent rats, quantifying locally evoked GABA A receptor-mediated inhibitory postsynaptic potentials (eIPSP). We examined the effects of taurine and alcohol on CeA eIPSP to characterize potential alcohol dependence-induced changes in the effects of taurine.Results: We found that taurine decreased amplitudes of eIPSP in CeA neurons of na€ ıve rats, without affecting the acute alcohol-induced facilitation of GABAergic responses. In CeA neurons from dependent rats, taurine no longer had an effect on eIPSP, but now blocked the ethanol (EtOH)-induced increase in eIPSP amplitude normally seen. Additionally, preapplication of the glycine receptor-specific antagonist strychnine blocked the EtOH-induced increase in eIPSP amplitude in neurons from na€ ıve rats.Conclusions: These data suggest taurine may act to oppose the effects of acute alcohol via the glycine receptor in the CeA of na€ ıve rats, and this modulatory system is altered in the CeA of dependent rats.

Development of the Heart Muscle after Antenatal Ethanol Intoxication during the Neonatal Period

“…The study of the problem of alcoholism is relevant. [1][2][3][4] Alcoholism affects the central nervous system, 5,6 cardiovascular, 7,8 and digestive systems. 9,10 Female alcoholism is especially dangerous, as its consequence is the birth of children with fetal alcohol syndrome (FAD).…”

Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats

“…We incubated CeA slices in an interface configuration for 15–20 min, and then completely submerged and continuously superfused them (flow rate of 2–4 ml/min) with 95% O 2 /5% CO 2 equilibrated artificial cerebrospinal fluid (aCSF) of the following composition (all in mM): 130 NaCl, 3.5 KCl, 1.25 NaH 2 PO 4 , 1.5mMMgSO 4 •7H 2 O, 2.0 CaCl 2 ; 24 NaHCO 3 , and 10 glucose. We recorded from 57 CeA (medial subdivision) neurons using sharp micropipettes filled with 3 M KCl in discontinuous current-clamp mode ( Kirson et al, 2020 ; Tunstall et al, 2019 ) holding them near their resting membrane potential (−80.2 ± 0.7 mV). We acquired data with an Axoclamp-2A amplifier (Axon Instruments, Foster City, CA) and stored them for off-line analysis with pClamp software (Axon Instruments).…”

Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses

“…All rats were housed in a temperature- and humidity-controlled room on a 12 h light/dark cycle with food and water available ad libitum. Alcohol-dependent rats (average blood alcohol level 172.68 ± 17.4 mg/dL at time of sacrifice) were generated by exposure to alcohol vapor daily (14 h alcohol vapor; 10 h air vapor) for 5–7 weeks [ 30 , 48 , 49 , 50 ] Female ( N = 6) and male ( N = 6) Wistar rats (Charles River, Raleigh, NC, USA) weighed on average 253.17 ± 12.7 g and 387.67 ± 24.5 g, respectively, at time of sacrifice. All procedures and care were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were reviewed and approved by the Institutional Animal Care and Use Committee of The Scripps Research Institute.…”